The overarching goal of this ICBG is to improve human health and well being through an integrated set of programs dedicated to the description, assessment, rational utilization, and conservation of biodiversity in Papua New Guinea (PNG). PNG is home to approximately 5% of the world's biodiversity. An understanding of the range of biological resources existing in PNG is essential for their management, for the preservation of species critical to indigenous cultures, and for the development of strategies for sustainable use. Our central hypothesis is that effective new therapeutics can be derived from the natural products of PNG's biological wealth. Such therapeutics can provide needed revenue to local stake-holders and responsible PNG institutions, and an incentive for the preservation of biological diversity. The university-based drug discovery component will focus on human immunodeficiency virus and Mycobacterium tuberculosis, while the industry based drug discovery component will focus on parasitic diseases, animal health and other therapeutic targets. The source organisms for drug discovery will be marine and terrestrial microbes and marine invertebrate animals. Documentation and preservation of traditional knowledge concerning medicinal plant use in PNG will be a second emphasis of this work. Medicinal plant surveys will be complemented by projects in support of the Traditional Medicines Taskforce, and student theses, to provide pharmacologic validation and chemical standardization of medicinal plants, and the identification of novel bioactive molecules. This research will provide professional development, educational opportunities and technology transfer for collaborating scientists and students. Conservation and biodiversity studies will center in the CTFS/SIGEO forest dynamics plot that has been established in Wanang, PNG, as part of the previous grant cycle's achievements. This plot is a unique and powerful research tool for studying forest dynamics, carbon sequestration and climate effects. Plot activities will integrate the botanical survey with the ecosystem study to include soil microbes and small plants. Outreach activities conducted as part of the Traditional Medicines and botanical survey work will foster the conservation and sustainable use of resources and provide benefits to stake-holders. Legislative initiatives developed with government input promote scientific exchange, conservation and sustainable resource use.